Expression changes of ER, PR, HER2, and Ki-67 in primary and metastatic breast cancer and its clinical significance.

Objective: To explore the altered expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and cell proliferation index (Ki-67) in primary and metastatic breast cancer lesions and the correlation between the primary tumor size, lymph node metastasis, Tumor Node Metastasis (TNM) stage, molecular typing, and disease-free survival (DFS) and their clinical significance. Methods: A retrospective analysis was conducted on the clinical data of 130 patients with metastatic breast cancer biopsy admitted to the Cancer Center of the Second Affiliated Hospital of Anhui Medical University in Hefei, China, from 2014-2019. The altered expression of ER, PR, HER2, and Ki-67 in primary and metastatic lesions of breast cancer was analyzed with respect to the site of metastasis, size of the primary tumor, lymph node metastasis, disease progression, and prognosis. Results: The inconsistent expression rates of ER, PR, HER2, and Ki-67 in primary and metastatic lesions were 47.69%, 51.54%, 28.10%, and 29.23%, respectively. The size of the primary lesion was not, but that accompanied by lymph node metastasis was related to the altered receptor expression. Patients with positive ER and PR expression in both primary and metastatic lesions had the longest DFS, while those with negative expression had the shortest DFS. Also, changes in HER2 expression in primary and metastatic lesions were not associated with DFS. Patients with low expression of Ki-67 in both primary and metastatic lesions had the longest DFS, while patients with high expression had the shortest DFS. Conclusion: Heterogeneity was detected in the expression levels of ER, PR, HER2, and Ki-67 in the primary and metastatic breast cancer lesions, which has a guiding significance for the treatment and prognosis of patients.

Improvement of coal gasification reverse osmosis concentrate treatment by Cu-Co-Mn/AC catalytic ozonation.

Approximately 20% of concentrate will be produced from coal gasification wastewater after reverse osmosis treatment. The organic matter contained in the concentrate affects its evaporation crystallisation; therefore, the refractory organics must be removed. In this study, Cu-Co-Mn/AC catalytic ozonation was used to treat reverse osmosis concentrate (ROC). With the addition of the Cu-Co-Mn/AC catalyst, the production of ·OH increased by 82 µmol/L, thereby enhancing the ozonation performance. The pH, ozone dosage, and catalyst dosage all affected the catalytic ozonation performance. By constructing a response surface model, it was found that the catalyst dosage had the most significant effect on the catalytic ozonation performance. The predicted optimal reaction conditions were pH = 9.02, ozone dosage = 1.08 g/L, and catalyst dosage = 1.33 g/L, under which the chemical oxygen demand (COD) removal reached a maximum of 81.49%.

Effects of different concentrations of CO2 on Scenedesmus obliquus to overcome sludge extract toxicity and accumulate biomass.

Large amounts of toxic excess sludge as well as high concentrations of carbon dioxide can be produced in coal-gasification industry. Microalgae has huge potential in the use of nutrients, the removal of toxic organic matter in excess sludge and CO2 fixation. At the same time, the cultivation of the microalgae and the accumulation of high-quality biomass are also the key problems of concern. In this study, the growth and biomass synthesis of Scenedesmus obliquus cultured in sludge extract under 0%-15% (v/v) CO2 were investigated. Results indicated that the highest microalgae biomass yield of 1.609 ± 0.012 g/L can be achieved under 15% CO2 on the 30th day. The maximal photochemical efficiency of PSⅡ (Fv/Fm) decreased in the first 12 h and then increased with the culture time, and the decline amplitude decreased with the increase of the CO2 concentration, indicating that CO2 slowed down the toxic inhibition of sludge extract to Scenedesmus obliquus, which was expressed as the down-regulation of p53 signaling pathway and protein A0A383WFI7. Proteomic analysis showed that under high-concentration CO2, the protein interaction network with the protein of photosystem II assembly (A0A383VSL5) as the core protein regulated the growth of Scenedesmus obliquus in terms of energy metabolism and material transportation. On the 4th day, Methyltransf_11 domain-containing protein (A0A383VH03) was up-regulated and promoted lipid synthesis, leading to the accumulation of lipids in Scenedesmus obliquus in the early stage and the increase of polysaccharides in the later stage. Collectively, this study revealed the regulation mechanism of CO2 on toxicity removal and carbon distribution of Scenedesmus obliquus.

Anlotinib plus nab-paclitaxel/gemcitabine as first-line treatment prolongs survival in patients with unresectable or metastatic pancreatic adenocarcinoma: a retrospective cohort.

Background: The timely addition of anlotinib to the nab-paclitaxel/gemcitabine regimen may further increase the treatment efficacy for pancreatic adenocarcinoma (PDAC), which has not yet been reported. Therefore, we aimed to compare the efficacy and safety of anlotinib plus nab-paclitaxel/gemcitabine in the first-line treatment of patients with unresectable or metastatic PDAC. Methods: This was a retrospective cohort of patients with unresectable or metastatic PDAC performed in The First Affiliated Hospital of Anhui Medical University from August 17, 2019 to April 3, 2021. Patients who received anlotinib plus nab-paclitaxel/gemcitabine treatment were defined as the anlotinib plus chemotherapy group and patients who received nab-paclitaxel/gemcitabine were defined as the chemotherapy group. The primary outcomes were progression-free survival (PFS) and overall survival (OS). Secondary outcomes were the objective response rate (ORR), the disease control rate (DCR), and toxic side effects. Clinical data and follow-up information were mainly obtained from hospital records or by telephone. Results: A total of 33 patients were included in this study, with 17 cases in the anlotinib plus chemotherapy group and 16 cases in the chemotherapy group. The median PFS (mPFS) of the anlotinib plus chemotherapy group was 5 months while the mPFS of the chemotherapy group was 2.7 months (P=0.0220). The median OS (mOS) of the anlotinib plus chemotherapy group was 9 months while the mOS of the chemotherapy group was 6 months (P=0.0060). The 3-month and 6-month PFS, and the 6- and 12-month OS of the anlotinib plus chemotherapy group were significantly higher than those of the chemotherapy group (P<0.05). The proportion of patients with hematological toxicities in the anlotinib plus chemotherapy group was not significantly higher than that in the chemotherapy group. Conclusions: Anlotinib plus nab-paclitaxel/gemcitabine as a first-line treatment regimen is safe and may prolong survival compared with nab-paclitaxel/gemcitabine chemotherapy in patients with unresectable or metastatic PDAC. Randomized controlled trials with large sample sizes are warranted to further evaluate the treatment effects of anlotinib in PDAC. Keywords: Pancreatic adenocarcinoma (PDAC); anlotinib; nab-paclitaxel/gemcitabine; progression-free survival (PFS); overall survival (OS).

Safety and efficacy of sintilimab combination therapy for the treatment of 48 patients with advanced malignant tumors.

Background: Sintilimab is a recombinant fully human anti-programmed death 1 (PD-1) monoclonal antibody that blocks the interaction of PD-1 with its ligand. We evaluated the safety and efficacy of sintilimab combined with chemotherapy and targeted therapy in the treatment of advanced malignant tumors. Methods: We performed a retrospective analysis of the clinical data of patients with advanced malignant tumors treated with sintilimab combined with chemotherapy and targeted therapy admitted to the Third Ward of the Department of Medical Oncology, First Affiliated Hospital of Anhui Medical University, China, from July 2019 to February 2021. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and related adverse reactions were analyzed. Results: A total of 48 patients with advanced malignant tumors treated with sintilimab combined with chemotherapy and targeted therapy. All 48 patients completed 2 courses of treatment, and the ORR and DCR were 20.83% and 81.25%. The median PFS for all patients in this study was 7 months, and the median OS was not yet reached. The median PFS for the first-line and second-line patients was 10 months, and the median OS was not yet reached. The median PFS for third-line and beyond patients was 7 months, and the median OS was 10 months. The differences in PFS and OS were both statistically significant. Adverse events occurred in 24 patients, of which 18 patients had grade I-II adverse events and 6 patients had grade III-IV adverse events. Conclusions: Sintilimab is an inexpensive PD-1 drug produced in China. Sintilimab combination therapy showed good safety in the treatment of advanced malignant tumors, with increases in the treatment efficacy and DCR for advanced tumors. Because of few adverse reactions and proven efficacy, sintilimab combination therapy can be used as an option for the treatment of advanced malignant tumors.

Bacterial diversity evolution process based on physicochemical characteristics of sludge treating hydroquinone during acclimation.

Hydroquinone is one of the main pollutants in coal-gasification wastewater, which is biologically toxic and difficult to remove. The aerobic biodegradation rate, organic toxicity, and microbial community structure at different acclimation stages of degradation of hydroquinone by activated sludge were investigated. In each acclimation cycle, the removal of hydroquinone reached 100% after 5 days, indicating that high-concentration hydroquinone in the activated sludge could be completely biodegraded. When the microbial flora was inhibited by the influent hydroquinone, the enzyme system experienced stress conditions and led to the secretion of secondary metabolites, extracellular protein of 5-10 kDa mainly contributing to the sludge organic toxicity. Microbial diversity analysis showed that with the increase of the concentration of hydroquinone, ß-Proteus bacteria such as Azoarcus and Dechloromonas gradually accumulated, which improved the removal of hydroquinone with aerobic activated sludge in the sequencing batch reactor (SBR) system. As the inhibition degree exceeded the appropriate tolerance range of microorganisms, bacteria would secrete much more secondary metabolites, and the organic toxicity of sludge would reach a relatively high level.

Study on the differences in sludge toxicity and microbial community structure caused by catechol, resorcinol and hydroquinone with metagenomic analysis.

The aerobic biodegradation rate, organic toxicity and microbial community structure of activated sludge acclimated by catechol, resorcinol and hydroquinone were investigated, to study the relationship between microbial structure and sludge organic toxicity caused by phenolic compounds. At the stable operation stage, the degradation rates of the dihydroxy benzenes in a single sequencing batch reactor (SBR) cycle were followed the order: resorcinol (89.71%) > hydroquinone (85.64%) > catechol (59.62%). Sludge toxicity bioassay indicated that the toxicity of sludge was catechol (45.63%) > hydroquinone (40.28%) > resorcinol (38.15%). The accumulation of secondary metabolites such as 5-10 kDa tryptophan and tyrosine protein substances caused the differential sludge toxicity. Microbial metagenomic analysis showed that the toxicity of sludge was significantly related to the microbial community structure. Thauera, Azoarcus, Pseudomonas and other Proteobacteria formed in the sludge during acclimation. Catechol group had the least dominant bacteria and loop ring opening enzyme genes (catA, dmpB, dxnF, hapD) numbers. Therefore, the degradation of catechol was the most difficult than resorcinol and hydroquinone, resulting the highest sludge toxicity.

IoT Adaptive Dynamic Blockchain Networking Method Based on Discrete Heartbeat Signals.

The combination of blockchain technology and Internet of Things (IoT) technology has brought many significant advantages and new development directions. With the development of embedded technology and 5G communication technology, the performance limitations and network limitations that are traditionally believed to restrict the application of blockchain technology to IoT devices have been broken. The development of "blockchain + 5G + IoT" provides reliable data from the source for the blockchain, linking the credible mapping of physical assets and digital assets. However, at the beginning of the blockchain design, the application of the IoT was not fully considered, so there have been some obvious defects in applying the blockchain technology in the IoT. In the Byzantine fault tolerance (BFT) consensus algorithm of traditional blockchain, the entire blockchain network will become paralyzed when more than 1/3 of the nodes in the network are offline. However, in IoT applications, this situation is likely to occur and greatly limits the security and stability of the application of blockchain technology in the IoT. In order to solve this problem, we proposed an IoT adaptive dynamic blockchain networking method based on discrete heartbeat signals. The feature of the method is to set a different monitoring time for each group of nodes, that is, discrete heartbeat signals monitoring. When the number of nodes gradually decreases, the IoT adaptive dynamic blockchain network can dynamically adapt to this process. Even when more than 1/3 of the IoT are offline, the adaptive dynamic IoT blockchain network can maintain stable running. This method also has the advantages of a short network expectation recovery time and avoids instantaneous system paralysis caused by the thundering herd effect. This research improves the security and stability of the application of blockchain technology in the IoT, and provides the necessary technical foundation for the better combination of blockchain technology and IoT technology.

Design and Test of a Microdestructive Tree-Ring Measurement System.

Analysis of a tree ring is the primary method for determining the growth and age of a tree. In a microdestructive tree-ring measurement system, the tree under test is drilled with a microdrill at a constant rotating speed to detect the difference in density between the early and late wood, thereby realizing a microdestructive measurement of the tree-ring. The measurement system comprises a microdrill with a diameter of 3 mm, mechanical transmission, direct current (DC) servomotor, stepper motor, and control and detection circuit. The DC servomotor and stepper motor realize rotation and translation of the microdrill, respectively, through mechanical transmission. When the microdrill rotates and drills into the tree, the control and detection circuit samples and acquires the armature current of the DC servomotor, which is proportional to the resistance encountered by the drill bit and reflects the change in the density of the tree. The tree-ring number can be obtained by filtering the sampled original signals of the armature current using a finite impulse response (FIR) filtering algorithm. The annual rings of larch and fir tree discs were measured and tested using the designed system. It was observed that the average annual ring measurement accuracy of the larch discs reached 95.28%, while that of the fir discs was 84.16%. The diameter of the drill hole in the trunk was less than 3 mm after measuring the living wood, thereby achieving a microdestructive measurement of the tree-ring.

Clinical efficacy analysis of Osimertinib treatment for a patient with leptomeningeal metastasis of EGFR+ non-small cell lung cancer without the T790M mutation.

BACKGROUND: To find the method of therapy of leptomeningeal metastasis (LM) to non-small cell lung cancer (NSCLC) patient with EGFR mutation (EGFR+) but without T790M mutation. METHODS: A retrospective analysis was reviewed for 5 NSCLC patients with EGFR+ who develop to LM from January 2018 to February 2019 in our hospital. RESULTS: All five NSCLC cases were adenocarcinoma, four cases were verified existed EGFR mutation with 19 exon deletion in the first diagnosed by biopsy tissue, the other tissue was verified 21 exon mutation. Two cases were initially diagnosed with LM, and the other three cases were found metastasis with leptomeningeal respectively after 64, 3 and 4 months when the lung cancer was diagnosed. There were not verified to exist T790M mutation with EGFR+ when all the five cases developed to LM. The major symptom was headache and blurred vision. In the image scanning, two cases were not revealed, but other three cases show that multiple metastatic lesions with brain and meninges. All patients were identified existed adenocarcinoma cells in cerebrospinal fluid (CSF). Four cases were treated by the first epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) and joint therapy including chemotherapy and radiotherapy, and the other case was treated by temozolomide and intrathecal chemotherapy in their earlier therapy. The curative effect was significant when they took osimertinib orally 80 mg once a day, for the disease progressing. The neurological symptoms were relieved in patient about 5-10 days after osimertinib treatment. The remission time was 10, 7, 7, 5, 4 months respectively until last following time to June 2019. The survival time was respectively 74, 7, 27, 18, and 4 months. The side effects were not increased. CONCLUSIONS: Whether EGFR+ with T790M mutation was positive or negative, osimertinib is an effective drug and can improve quality of life and prolong the survival for NSCLC patient with EGFR mutation to progress LM.

A significant carbon sink in temperate forests in Beijing: based on 20-year field measurements in three stands.

Numerous efforts have been made to characterize forest carbon (C) cycles and stocks in various ecosystems. However, long-term observation on each component of the forest C cycle is still lacking. We measured C stocks and fluxes in three permanent temperate forest plots (birch, oak and pine forest) during 2011­2014, and calculated the changes of the components of the C cycle related to the measurements during 1992­1994 at Mt. Dongling, Beijing, China. Forest net primary production in birch, oak, and pine plots was 5.32, 4.53, and 6.73 Mg C ha-1 a-1, respectively. Corresponding net ecosystem production was 0.12, 0.43, and 3.53 Mg C ha-1 a-1. The C stocks and fluxes in 2011­2014 were significantly larger than those in 1992­1994 in which the biomass C densities in birch, oak, and pine plots increased from 50.0, 37.7, and 54.0 Mg C ha-1 in 1994 to 101.5, 77.3, and 110.9 Mg C ha-1 in 2014; soil organic C densities increased from 207.0, 239.1, and 231.7 Mg C ha-1 to 214.8, 241.7, and 238.4 Mg C ha-1; and soil heterotrophic respiration increased from 2.78, 3.49, and 1.81 Mg C ha-1 a-1 to 5.20, 4.10, and 3.20 Mg C ha-1 a-1. These results suggest that the mountainous temperate forest ecosystems in Beijing have served as a carbon sink in the last two decades. These observations of C stocks and fluxes provided field-based data for a long-term study of C cycling in temperate forest ecosystems.